Lipid Levels and Use of Lipid-Lowering Drugs for Patients in Pharmacist-Managed Lipid Clinics Versus Usual Care in 2 VA Medical Centers

OBJECTIVES: The objective of this study was to assess the effectiveness of pharmacist-managed dyslipidemia clinics at 2 Veterans Affairs medical centers since the release of the 2001 National Cholesterol Education Panel Adult Treatment Panel III (NCEP ATP III) guideline compared with the usual care (UC) provided by other health care professionals in the same setting. METHODS: Analysis was performed through retrospective chart review of patients with a diagnosis of dyslipidemia who received care in either the Amarillo or Lubbock, Texas, pharmacist-managed lipid clinics (LCs) or UC from a primary care physician. Data from medical charts were abstracted for dates of service from July 2001 to December 2003 for 115 patients selected randomly from LC rolls matched with 115 patients with a diagnosis of dyslipidemia selected randomly from UC. All patients had to have had at least 3 visits with the LC or 3 visits in UC with a billing code of dyslipidemia; they were followed for at least 6 months after an initial visit in July 2001 or thereafter and were enrolled in the VA health care system for at least 1 year. Baseline lipid values were available for LC but not UC patients. Cholesterol target goals were determined according to NCEP ATP III guideline. RESULTS: After an average of 21.6 months of follow-up, the proportion of patients in the LC group that attained goal level increased from 45.2% at baseline to 82.6% for total cholesterol (TC) and from 36.5% at baseline to 64.3% for low density lipoprotein cholesterol (LDL-C [P less than 0.001 for both comparisons]). There was an average 24.5 mg/dL absolute reduction (relative reduction, 19.4%) in LDL-C along with significant improvements in the other lipid levels (P>0.001 for TC and LDL-C, P = 0.007 for triglycerides [TGs]) with the exception of high density lipoprotein cholesterol (HDL-C), which declined from 40.0 mg/dL to 36.3 mg/dL (P less than 0.001). A total of 50 patients (43.5%) were on lipid-lowering pharmacotherapy at baseline versus 108 patients (93.9%) at follow-up. Compared with UC, LC patients were more likely to have achieved goal LDL-C (64.3% vs. 15.7% for UC, P less than 0.001) and TC (82.6% vs. 40.9%, P less than 0.001), but there was no difference in the proportion of patients at TG goal for LC (65.2%) compared with UC (52.2%, P=0.061) or at HDL-C goal (23.5% for LC vs. 33.0% for UC, P=0.143). A higher proportion of LC patients (93.9%) used lipid-lowering agents compared with UC patients (24.3%, P less than 0.001). Subanalysis of patients on a lipid-lowering agent found that a significantly higher proportion (85.2%) in the LC group were at goal total cholesterol compared with 60.7% for UC (P=0.012) and at goal LDL-C (66.7% for LC vs. 39.3% for UC, P=0.016). However, a lower proportion were at goal HDL-C for LC (21.3%) versus 42.9% for UC (P=0.043). Overall, only 11 LC patients (9.6%) attained goal levels for all 4 serum lipid values by the end of follow-up versus 2 UC patients (1.7%, P=0.019). CONCLUSIONS: Nearly two thirds of patients diagnosed with dyslipidemia and enrolled in a pharmacist-managed LC had LDL-C levels at or below NCEP ATP III target goal compared with 16% of dyslipidemia patients who received UC from their primary care provider. The pharmacist-managed LC patients were also twice as likely (83 vs. 41%) to have attained the TC target goal, but there was no difference between the 2 groups in the proportion of patients who attained either TG or HDL-C target goals. Only 9.6% of LC patients were at goal for all 4 individual lipid measures at the end of follow-up.

medication use, although those who do receive drug therapy are more likely to reach these goals. 10,11 Shortly after publication of NCEP ATP III guidelines in 2001, a group of investigators evaluated the impact of these guidelines versus the previous NCEP ATP II guidelines on a sample of NHANES III participants with known cardiovascular risk factors. 12 The investigators found a 140% increase in the number of patients eligible for LDL-C-lowering therapy, a 157% increase among males versus a 122% increase among females.
Among the ever-expanding roles pharmacists perform in the health care system, collaborative drug therapy management is one particular role where pharmacists can have a significant impact in improving patient care outcomes. Studies assessing the impact of pharmacist management of dyslipidemia have shown improved lipid goal attainment and appropriate medication use either compared with a baseline or a control group. [13][14][15][16][17][18][19][20] However, only one of these studies was performed on intermediate outcomes that occurred after the release of the most recent NCEP guidelines in 2001. 20 These guidelines significantly altered LDL-C goals for patients newly classified as having an increased risk for a CHD event (e.g. diabetics and those with a >20% 10-year risk), altered classifications for other lipid parameters (e.g., triglycerides [TGs] and high-density lipoprotein cholesterol [HDL-C]), and increased the number of patients who require lipid-lowering therapy as a result. 7 Quilliam et al. found that 21% of 1,962 managed care organization (MCO) patients on a statin drug moved to a more stringent LDL-C goal when the ATP III criteria were applied over ATP II, and substituting the ATP III criteria for ATP II criteria resulted in a 7% decrease in the percentage of patients who had their most recent LDL-C value below the suggested goal, from 69% under ATP II to 53% under ATP III. 21 The objective of this study was to compare the outcomes of care provided by the pharmacistmanaged clinic with the care provided by other health care professionals in the same setting in the context of the NCEP ATP III guidelines.

Design and Patient Selection
This study was a retrospective review of medical charts for patients who received lipid management care at the Veterans Administration Medical Center (VAMC) in Amarillo, Texas, or the Lubbock, Texas, VA Outpatient Clinic. The population served by the VAMC in Amarillo is approximately 95,000 and approximately 63,000 at the Outpatient Clinic in Lubbock. The study design was approved by the Texas Tech University Health Sciences Center Institutional Review Board and the Amarillo VA Research and Development Committee.
The pharmacist-managed referral lipid clinics (LCs) at these sites were initiated in 1995 and, combined, they currently serve more than 3,500 patients. Patients are referred for enrollment in the LC after a diagnosis of dyslipidemia has been made by their primary care provider. Patients are typically referred to the LC with abnormal lipid levels and/or a history of CHD. The referral process is voluntary, and the primary care provider can manage the patient' s dyslipidemia without the involvement of the LC. Primary care providers at these VAMC' s are composed of physicians, physician assistants, and nurse practitioners.
Patients included in the LC group were randomly selected from a generated list of all patients who had been seen in the lipid education class between July 2001 and December 2003. This time period was chosen to coincide with the publication of the NCEP ATP III Executive Summary to make sure that all patients without known CHD would be evaluated for the presence of other CHD REs. Patients included in the usual care (UC) groups were randomly selected from a generated list of patients seen by a primary care provider with an International Classification of Disease, Ninth Revision (ICD-9) code for dyslipidemia ( . Criteria for inclusion into the study were as follows: had a diagnosis of dyslipidemia; had a minimum of 3 visits with the pharmacistmanaged specialty clinic or 3 visits with the primary care provider, with an ICD-9 billing code listed above; were followed in either clinic for at least 6 months with an initial clinic visit on or after July 2001; and were enrolled in the VA health care system for at least 1 year. Patients were excluded from the study if they had documented noncompliance in their medical records as defined by missing 2 or more scheduled routine appointments. Patients were also excluded if they had a thyroid-stimulating hormone level >4.5 m IU/ml at any time during study period, to eliminate patients with uncontrolled hypothyroidism. Charts were reviewed until there were 115 patients in each group.

The Lipid Clinic Intervention
Upon enrollment in the LC, the clinical pharmacists assessed and treated the patients' dyslipidemia to achieve goal lipid levels based on the NCEP ATP III guideline and recent recommendations. 7,22 The clinical pharmacists in these clinics have prescribing authority for all VA formulary lipid-lowering agents. Any changes made to lipid-lowering medications can be performed only by one of the clinical pharmacists once the patient has been enrolled in the LC.
The initial visit to the specialty LC included an educational class session where the patients received information about the treatment of dyslipidemia and therapeutic lifestyle modifications. Education at these classes was provided by a dietitian and one of the clinic pharmacists. After this visit, patients were scheduled for appropriate follow-up visits (20-minute appointments) in the LC, during which the patient' s lifestyle (diet and exercise), changes in health status, and current lipid profile were reviewed with the patient and any necessary changes in lipidlowering medications were made. Patients were discharged from the clinic after they had achieved and maintained goal lipid levels for 2 or more consecutive clinic visits and no longer required the focused services of the specialty clinic.

Outcome Measures
The primary outcomes of this study were the absolute values and the percentage changes in serum LDL-C at the most recent fasting lipid panel (FLP) and the proportion of patients who attained goal LDL-C for the LC compared with UC and for the LC group compared with baseline. Secondary outcomes of interest included the absolute values and percentage changes in the other FLP values and the proportions of patients who attained, goal TC, HDL-C, TGs, TC to HDL-C ratio (TC/HDL-C), and non-HDL-C. A Framingham risk analysis score was calculated for all patients with no known history of CHD or other CHD RE and 2 or more CAD risk factors. Calculation was performed with the Web-based Framingham risk calculator provided by the National Heart, Lung, and Blood Institute (http://hin.nhlbi.nih.gov/atpiii/calculator.asp).

Data Collection
Electronic medical records were reviewed and data were collected as described below. Patient' s age, gender, and weight were recorded for the patient' s most recent visit. The most recent FLP values were recorded for the LC and UC groups, and the FLP values at enrollment in the pharmacist-managed specialty clinic (baseline) were recorded. CHD or CHD RE diseases (e.g., myocardial infarction, diabetes) and coronary artery disease risk factors (e.g., tobacco use, hypertension), as defined by NCEP III guidelines, were recorded. The number of clinic visits and duration of enrollment in the clinic (months) were recorded to determine the number of visits per year. Use of a lipid-lowering agent was determined through review of electronic medical records as well as documentation in any clinic note that the patient was using an agent obtained outside of the VA from a private physician.

Data Analysis
The data are presented as mean ± standard deviation or as proportions when appropriate. When available, a 95% confidence interval is presented. This study required 80 patients in each group to have an 80% power to detect a 20% difference in the primary outcome (percentage obtaining goal LDL-C) between LC and UC (α = 0.05). All statistical analyses were performed using Analyse-It version 1.71 electronic software (Leeds, United Kingdom). All comparisons of nominal data were performed using chi-square or Fisher' s exact test when appropriate. For comparison of all continuous variables, the assessment of the LC for values at the most recent visit compared with baseline was done using a paired t test. When these variables were not normally distributed, comparisons were made using a Wilcoxon signed rank test. Comparisons of all continuous variables between groups were performed with the Student' s t test. If these variables were not normally distributed, comparisons were made using a Mann-Whitney U test. A P value of <0.05 was considered significant.

LC and UC Comparison Analysis
There were 115 patients in the LC group and 115 in the UC group. Patient characteristics were similar between the groups with the exception of the percentage of patients who had documented tobacco use, a documented family history of premature heart disease, and a low HDL-C (Table 1). There were no differences in the type of CHD or CHD RE diseases between the groups. The annual number of clinic visits was not significantly different between patients enrolled in the LC (2.97) and UC (2.98) group (P = 0.055).
All measured lipid levels at the most recent FLP were found to be significantly lower in patients enrolled in the LC ( Table 2): 48.6% more patients in the LC were at goal LDL-C compared with UC (64.3% vs. 15.7%, P <0.001). Significant differences were also seen in TC and those at all goal lipid levels (P <0.001 and P = 0.019, respectively), but not in the proportion at goal HDL-C (P = 0.143), and the UC group had a significantly higher mean HDL-C (39.0 vs. 36.2 for LC, P <0.001) Use of a lipid-lowering agent was found in 28 patients (24.3%) in the UC group compared with 108 (93.9%) in the LC group, nearly a 4-fold difference (Table 3). Based on the large difference in medication use between the groups, further analysis was performed evaluating the same outcomes in those patients from both LCs that were known to be on one or more lipid-lowering agents. The proportion attaining goal LDL-C in the LC group remained significantly different compared with UC, 66.7% versus 39.3%, a 27.4% absolute difference between the groups (P = 0.016).
Further analysis was performed between and within both groups for patients who had a Framingham 10-year analysis risk score calculated. For 20 patients in LCs and 26 patients in UC with a Framingham risk score >20%, the LC patients had lower absolute TC, LDL-C, and TG values but not higher HDL-C values (Table 4). For the proportion of patients at goal, the LC patients were more likely to be at goal for TC, LDL-C, and TGs but not for HDL-C or for all 4 values.
The mean age for the 115 LC patients who satisfied the inclusion criteria was 67.9 years. The group included only 2 females and 85.2% had CHD or a CHD RE disease ( Table 1). The mean duration of enrollment in the clinic was 21.56 ± 5.2 months, with an average of 5.16 ± 1.3 visits to clinic (data not presented). Compared with baseline, TC, LDL-C, HDL-C, and TGs were reduced by 16.2%, 19.5%, 9.3%, and 14.6%, respectively (TC, LDL-C, and HDL-C, P <0.001; TGs, P=0.007) ( Table 5)

CI = confidence interval; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TC/HDL-C ratio = total cholesterol to high-density lipoprotein cholesterol ratio; TG = triglycerides.
lipid-lowering drug therapy. A total of 11 patients (9.6%) were found to be at all goal lipid levels at the most recent visit (P = 0.639). At baseline, 50 patients (43.5%) were on lipidlowering pharmacotherapy versus 108 patients (93.9%) at the most recent LC visits, an increase of 116% (P <0.001, data not presented in tables).

II Discussion
To our knowledge, this report is the first published study evaluating the effectiveness of a pharmacist-managed LC in the treatment of patients with dyslipidemia, including those without known CHD or CHD REs, based on NCEP ATP III guidelines. The findings of this study demonstrated significant improvements in the level of care provided to patients enrolled in the pharmacistmanaged LCs as defined by the proportion of patients who attained goal lipid levels at follow-up compared with baseline for TC and LDL-C but not for HDL-C, TGs, or patients at goal for all 4 serum lipid values. Comparison of these patients to randomly identified patients who were treated in UC by the primary care provider demonstrated significantly lower lipid levels, a higher percentage of patients achieving goal TC and LDL-C, and a greater utilization of lipid-lowering agents; there was no difference for LC versus UC for the proportion of patients at goal for HDL-C or TGs. Therefore, by these outcomes, the pharmacist-managed clinics were able to make effective drug therapy selection as well as provide important lifestyle education, resulting in a larger proportion of patients attaining LD and TC goals of therapy compared with UC.
The results of the subgroup analysis of patients with a  calculated Framingham CHD risk score showed significant differences between the LC and UC patients, with a Framingham risk score >20%. Perhaps the health care providers in the UC group are not utilizing the Framingham risk analysis score as a clinical tool in the care of their patients. On the other hand, only 50% of the LC patients with a Framingham risk score >20% attained LDL-C goal, only 10% attained HDL-C goal, and only 5% attained all 4 serum lipid goals.

Comparison of Lipid Clinic and Usual Care Patients on a Lipid-Lowering Medication*
Patients enrolled in the LC had a significant decrease in mean HDL-C levels. This is an unfavorable outcome in these patients, but there were offsetting favorable findings in the significant decrease in the non-HDL-C and a significant increase in the TC/HDL-C ratio. Overall, there were generally favorable serum lipid values for the LC patients, with a presumed lowering of the CHD risk in these paients.
The results of our study are in accordance with other previously published results in similar settings. Bozovich et al. prospectively evaluated the level of care provided by a pharmacistmanaged LC as compared with standard care provided by cardiologists in the same private practice clinic in the treatment of patients with a known history of CHD. 18 The investigators found that after 6 months of treatment, 69% of patients enrolled in the LC were at goal LDL-C compared with 50% of patients being treated by the cardiologists (P = 0.016), which compares favorably with our finding of 64.3% of LC patients but much higher for UC patients in Bozovich et al. (50%) compared with 16% in the present study. Bozovich et al. attributed the significant difference to more aggressive treatment and follow-up for patients enrolled in the pharmacist-managed LC.
Cording et al. investigated the efficiency of their pharmacistmanaged LC approximately 12 months after its inception in the treatment of patients with dyslipidemia; there was no comparison with a control group. 14 The proportion of patients attaining goal LDL-C based on the NCEP ATP II guidelines 23 increased from 40% at enrollment to 77% at the most recent visit, a 92.5% relative increase (P value was not provided).
A study with a similar design and similar outcomes by O'Donnell et al. found that 73% of patients enrolled in their pharmacist-managed LC were at goal LDL-C 16 compared with 64.3% in the present study. O'Donnell et al. concluded that patients were more likely to achieve and maintain goal LDL-C in their clinic if (1) the goal was attained in the clinic, (2) the patient had known CHD (i.e., lipid-lowering pharmaco-therapy for secondary prevention), and (3) the patient had fewer risk factors.
Geber et al. compared the care provided by their pharmacist-managed pharmacotherapy clinic with that provided by primary care providers at their institution in patients with a known history of CHD and a baseline LDL-C above goal (100 mg/dL) level. 13 The proportion of patients attaining NCEP LDL-C goal (<100 mg/dL) in the pharmacist-managed clinic was 72% compared with 39% in the primary care group (P <0.001).

Mean Change
An additional 18% of patients in the pharmacist-managed clinic were on a lipid-lowering medication (P value was not provided).
Till et al. compared a pharmacist-managed LC versus UC provided by primary care providers in the primary care clinics at the William Jennings Bryan Dorn VA Medical Center in South Carolina. 20 They evaluated 47 patients in the pharmacistmanaged group and 41 patients in the UC group. There was an 18.5% reduction in LDL-C in the pharmacist-managed patients compared with a 6.5% reduction in those patients treated in the UC group (P = 0.049). In that study, the mean LDL-C between the 2 groups was not found to be significantly different. However, the magnitude of LDL-C reduction was found to be related to the number of clinical pharmacy visits in a fairly linear manner and statistically different from the nonlinear relationship of LDL-C reduction and the number of UC visits (P = 0.038). Similar to the findings of our study, the proportion of patients with goal HDL-C (>40 mg/dL) was significantly lower in the pharmacist-managed patients (36%) compared with UC patients (56%, P = 0.037).
The multicenter IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) Study investigated efficacy of pharmacist-managed ambulatory care clinics in the treatment of a multitude of problems as compared with care provided by a control group of primary care providers. 24 The investigators found that 39.5% of patients with known CHD in the pharmacistmanaged clinics were at goal LDL-C compared with 34.5% of those receiving UC.

Limitations
The foremost limitation of the present study was the absence of baseline fasting lipid panel values for patients enrolled in the UC group. This limitation makes the precomparison and postcomparison for the LC group more robust than the comparison of the LC with the UC group. For the patient characteristics other than lipid values, the LC group and the UC group were significantly different. The UC group had a much higher proportion of use of tobacco (30.4% vs. 16.5%, P = 0.02) but a lower proportion with a family history of premature heart disease (7.0% vs. 19.1%, P = 0.011). The lower proportion of patients in the UC group with a family history of premature heart disease may explain the lower use of lipid-lowering drugs in this group.
Second, these study results are not generalizable since the patient population served at these 2 VA clinics is predominantly male and older than patients in most private MCOs. Third, we did not measure medication compliance in this study, and it is also possible that some of the patients obtained a lipid-lowering agent outside of the VA system that was not documented in the medical record. Fourth, the retrospective chart review did not permit elimination of the possibility that the recorded lipid values could have been nonfasting (i.e., there was no documentation in the record to confirm that the patient followed the explicit instructions to fast 8 to 12 hours prior to the medical visit to determine serum lipid values). There is also the possibility that the primary care provider could have deferred lipid management in patients who were concurrently seeing a private physician and/or specialist.
This study measured only the intermediate clinical outcomes of serum lipid values. There was no assessment of direct and administrative costs of providing pharmacist-managed LC services. Therefore, it was not possible to estimate a return on investment or to suggest that the pharmacist-managed LC service was cost effective.
Despite these limitations, the effectiveness of pharmacistmanaged specialty clinics has been demonstrated in numerous studies establishing the ability of similar specialty clinics to deliver appropriate care based on specific goals of therapy. [13][14][15][16][17][18][25][26][27][28] These clinics are likely successful because of their ability to have a focused visit devoting the majority of time on patient assessment and education. 29 In addition to these factors, the pharmacist services have demonstrated significant cost savings to both the patient and the health care organization. 30-32 A pharmacist' s time is often less costly to the patient and health care organization than is a physician' s. Thus, if a pharmacist is able to achieve a similar or improved level of care in treating a specific disease state, then a pharmacist-managed specialty clinic could be a cost-effective method to improve the efficiency of a health care system.
Based largely on these factors, physicians have voiced support of collaborative drug therapy management agreements between themselves and appropriately trained pharmacists. 33 Yet, there are additional potential roles for pharmacists in the treatment and identification of patients with dyslipidemia. 29,34 Such roles outside of drug therapy management can include providing education to patients and health care providers, community screening projects, and the traditional role of dispensing medications. Community pharmacists are a source of information for many patients, giving the pharmacist numerous educational opportunities. In a community setting, the access to pharmacists has been associated with significant improvements in the level of care provided to patients with dyslipidemia through screening projects and recommendations provided to the patients' primary care providers. 10,[35][36][37]

II Conclusions
The operation of pharmacist-managed LCs was associated with improved serum lipid values of enrolled patients compared with baseline for 5 of 6 measures and for the proportion of patients at goal levels for TC and LDL-C but not for HDL-C, TGs, or for all 4 goal levels. A smaller proportion of patients in the UC group, treated only by their primary care provider, received drug therapy for their dyslipidemia, contributing to a comparatively higher proportion of patients in the LC group that attained goal lipid levels. After nearly 2 years of follow-up, these 2 pharmacist-managed VA LCs had an effect on some but not all lipid panel values for enrolled patients. These pharmacistmanaged LCs, in which pharmacists had prescribing authority for referred patients, received more pharmacotherapy for dyslipidemia compared with UC groups.